Aging is a progressive decline in biological function characterized by increased susceptibility to disease. Advances in our understanding of the basic biology of aging will promote development of treatments to reduce the prominence of aging-related diseases and improve human health. Neurosensory systems and neuroendocrine signaling transduce nutrient signals and modulate organismal function to regulate aging, but the underlying mechanisms are poorly understood. Disruption of nutrient signals leads to many diseases, such as type II diabetes, cardiovascular disease and cancer. We hypothesize that neurosensory inputs signal through neuroendocrine systems to modulate organismal physiology and lifespan. The broad long-term objective of this project is to elucidate how neuronal systems use nutrient status to modulate aging. As Drosophila is a powerful model for dissecting genetic and neurobiology pathways, we will use Drosophila to investigate neuronal systems in physiological modulation of lifespan. First, we will test for genetic interactions between diet and neuroendocrine signals. Then, we will manipulate neurosensory pathways and determine whether nutrient status is transduced through neuroendocrine systems to regulate lifespan. Finally, we will characterize how specific neurosensory signals modulate aging. This work will set a foundation for elucidating mechanisms underlying neuronal control of metabolic processes and behaviors which affect aging. These studies will examine behavioral and environmental factors affecting aging, and reveal changes that can easily be implemented into daily life to improve human health and decrease the frequency of disease onset with age. PUBLIC HEALTH RELEVANCE:Aging is major risk factor for increased susceptibility to cancer, heart diseases, neurological diseases, and disorders which lead to poor health and loss of independence. Diet modulates physiology and aging, and elucidation of the underlying mechanisms will lead to interventions to prevent health-related deteriorations and reduce the frequency of aging-related diseases. The current proposal will test the hypothesis that nutrient signaling can be modulated to prevent aging-related declines in health.